I-haloethyl



Patented Nov. 13, 1962 7 3,064,005 l-HALOETHYL, S-AMINQ-PYRAZOLECARBONITRILES-( l) Jean Druey, Riehen, and Paul Schmidt, Therwil,Switzerland, assignors to Ciba Corporation, a corporation of Delaware NoDrawing. Filed Nov. 25, 1959, Ser. No. 855,274

Claims priority, application Switzerland Dec. 5, 1958 2 Claims. (Cl.260-310) This invention provides new pyrazoles and a process for theirmanufacture.

The new compounds are amino-pyrazoles of the formula i H N Ha-Cl The newcompounds are prepared by methods known per se.

One embodiment of the process of the invention consists in that inZ-(fl-R-ethyl)-3aamino-4-cyanopyrazole in which R represents a radicalreplaceable by a halogen atom, this radical is so replaced. Thusprefer-ably 2- (,G-hydroxyethyl)-3-amino-4-cyano-pyrazol is used asstarting material and treated with halogenating agents, advantageouslywith acid halides of sulfur or phosphorus, primarily thionyl chloride,phosphorus oxychloride or phosphorus pentachloride.

Another embodiment of the process of the invention consists in that in2-(B-hal0gen-ethyl)-3 amino-4-R'-pyra- 201 in which R represents asubstituent replaceable by the cyano group, this substituent is replacedby the cyano group. As such a substituent is primarily concerned thecarboxylic acid amide group, which can be converted by treatment withagents splitting off water, such as phosphorus pentoxide into the cyanogroup.

The above two embodiments can also be combined. Thus 2-(fl-hydroxy-ethyl) -3-amino-4-carbamyl pyrazole can be used as startingmaterial and in one operation, for example with phosphoruspentachloride, both the nitrile group formed and the halogen atomintroduced.

The starting materials are known or can be prepared by methods known perse. They can also be formed under the reaction conditions.

The invention also comprises any modification of the process in which acompound obtainable as an intermediate at any stage of the completeprocess is used as starting material and the remaining step or steps arecarried out or in which the process is interrupted at any stage.

The new compounds of the invention can be used in the form ofpharmaceutical preparations. These contain the said compounds inadmixture with a pharmaceutical organic or inorganic excipient suitablefor enteral or parenteral administration. As such are concernedsubstances that do not react with the described compounds, for examplewater, gelatine, lactose, starch, magnesium stearate, talc, vegetableoils, benzyl alcohols, giuns, polyalkylene glycols, cholesterol or otherknown excipients. The pharmaceutical preparations can, for example takethe form of tablets or dragees or can be prepared in fluid form assolutions, suspensions or emulsions. If desired they are sterilized and/or contain auxiliary substances such as preserving, stabilizing, wettingor emulsifying agents. They can also contain other therapeuticallyvaluable substances. The preparations are produced by customary methods.

The following example illustrates the invention:

Example A solution of 15.2 grams of 2-'(,8-hydroxyethyl)-3-amino-4-cyano-pyrazole in cc. of thionyl chloride is heated for twohours to 5060 C. The thionyl chloride is evaporated off under vacuum,the residue treated with ice Water and a pH 8 established with N-sodiumhydroxide solution. The deposited precipitate is then filtered withsuction and recrystallized from ethanol.Z-(B-chlorethyl)-3-amino-4-cyano-pwazole of theformula NC IT. HzNlN iOH:

Hr-Cl of the formula N C W HzNlN (:JHn CHz-OH is thus obtained in yellowcrystals of M.P. 156-158 C.

What is claimed is: 1. Amino-pyrazoles of the formula in hm Hz-Halwherein Hal represents a halogen atom.

2. 2-(fl-chloro-ethyD-3-amino-4-cyano-pyrazole.

No references cited.

1. AMINO-PYRAZOLES OF THE FORMULA